He joined the faculty of INPG in 1980, and left in 1984 to join the Industry and Technology for Machine Intelligence (ITMI), a company he co-founded in 1982. In 1987, Latombe joined Stanford University as an Associate Professor, and have since been the Professor (1992), Chairman (1997–2000), and Kumagai Professor (2001–Present) in the Department of Computer Science.

Latombe is an important figure in robotic motion planning. After Mark Overmars published the Probabilistic Roadmap Method (PRM) in 1992, Latombe and Lydia Kavraki independently developed the algorithm in 1994, and their joint paper with Overmars, Probabilistic roadmaps for path planning in high-dimensional configuration spaces,[2] is considered one of the most influential studies in motion planning, and has been widely cited (more than 1000 times as of 2008). More recently, Latombe has applied his knowledge in robotics to structural biology problems, and developed the PRM-based Stochastic Roadmap Simulation (SRS) to efficiently generate and analyze large collections of protein trajectories.[3]